Ulcerative colitis (UC) arises from a complex interplay between host and environmental factors, but with a largely unsolved pathophysiology. The pathophysiology was outlined by RNA-sequencing of mucosal biopsies from non-inflamed and inflamed colon of UC patients (14 and 17, respectively), and from 27 patients without intestinal inflammation. Genes differentially expressed (DE), or present in enriched gene sets, were investigated using statistical text analysis of functional protein information. Compared with controls, inflamed and non-inflamed UC mucosa displayed 9360 and 52 DE genes, respectively. Seventy-three non-pseudogenes were DE relative to both gender and inflammation. Mitochondrial processes were downregulated in inflamed and upregulated in non-inflamed UC mucosa, whereas angiogenesis and endoplasmic reticulum (ER) stress were upregulated in both tissue states. Immune responses were upregulated in inflamed mucosa, whereas the non-inflamed UC mucosa presented both up- and downregulated gene sets. DE and enriched genes overlapped with genes present in inflammatory bowel disease genome-wide associated loci (p = 1.43 × 10-18), especially regarding immune responses, respiratory chain, angiogenesis, ER stress, and steroid hormone metabolism. Apart from confirming established pathophysiological mechanisms of immune cells, our study provides evidence for involvement of less described pathways (e.g., respiratory chain, ER stress, fatty-acid oxidation, steroid hormone metabolism and angiogenesis).
Keywords: RNA sequencing; RNA-seq; differentially expressed genes; gene set enrichment analysis; intestinal mucosa; text analysis; transcriptome; ulcerative colitis.